Association of a device-based remote management heart failure pathway with outcomes: TriageHF Plus real-world evaluation.

AIMS: Clinical pathways have been shown to improve outcomes in patients with heart failure (HF). Although patients with HF often have a cardiac implantable electronic device, few studies have reported the utility of device-derived risk scores to augment and organize care. TriageHF Plus is a device-based HF clinical pathway (DHFP) that uses remote monitoring alerts to trigger structured telephone assessment for HF stability and optimization. We aimed to evaluate the impact of TriageHF Plus on hospitalizations and describe the associated workforce burden. METHODS AND RESULTS: TriageHF Plus was a multi-site, prospective study that compared outcomes for patients recruited between April 2019 and February 2021. All alert-triggered assessments were analysed to determine the appropriateness of the alert and the workload burden. A negative-binomial regression with inverse probability treatment weighting using a time-matched usual care cohort was applied to estimate the effect of TriageHF Plus on non-elective hospitalizations. A post hoc pre-COVID-19 sensitivity analysis was also performed. The TriageHF Plus cohort (n = 443) had a mean age of 68.8 ± 11.2 years, 77% male (usual care cohort: n = 315, mean age of 66.2 ± 14.5 years, 65% male). In the TriageHF Plus cohort, an acute medical issue was identified following an alert in 79/182 (43%) cases. Fifty assessments indicated acute HF, requiring clinical action in 44 cases. At 30 day follow-up, 39/66 (59%) of initially symptomatic patients reported improvement, and 20 (19%) initially asymptomatic patients had developed new symptoms. On average, each assessment took 10 min. The TriageHF Plus group had a 58% lower rate of hospitalizations across full follow-up [incidence relative ratio: 0.42, 95% confidence interval (CI): 0.23-0.76, P = 0.004]. Across the pre-COVID-19 window, hospitalizations were 31% lower (0.69, 95% CI: 0.46-1.04, P = 0.077). CONCLUSIONS: These data represent the largest real-world evaluation of a DHFP based on multi-parametric risk stratification. The TriageHF Plus clinical pathway was associated with an improvement in HF symptoms and reduced all-cause hospitalizations.

Correction: Impact of maintaining serum potassium concentration ≥ 3.6mEq/L versus ≥ 4.5mEq/L for 120 hours after isolated coronary artery bypass graft surgery on incidence of new onset atrial fibrillation: Protocol for a randomized non-inferiority trial.

[This corrects the article DOI: 10.1371/journal.pone.0296525.].

Impact of maintaining serum potassium concentration ≥ 3.6mEq/L versus ≥ 4.5mEq/L for 120 hours after isolated coronary artery bypass graft surgery on incidence of new onset atrial fibrillation: Protocol for a randomized non-inferiority trial.

BACKGROUND: Atrial Fibrillation After Cardiac Surgery (AFACS) occurs in about one in three patients following Coronary Artery Bypass Grafting (CABG). It is associated with increased short- and long-term morbidity, mortality and costs. To reduce AFACS incidence, efforts are often made to maintain serum potassium in the high-normal range (≥ 4.5mEq/L). However, there is no evidence that this strategy is efficacious. Furthermore, the approach is costly, often unpleasant for patients, and risks causing harm. We describe the protocol of a planned randomized non-inferiority trial to investigate the impact of intervening to maintain serum potassium ≥ 3.6 mEq/L vs ≥ 4.5 mEq/L on incidence of new-onset AFACS after isolated elective CABG. METHODS: Patients undergoing isolated CABG at sites in the UK and Germany will be recruited, randomized 1:1 and stratified by site to protocols maintaining serum potassium at either ≥ 3.6 mEq/L or ≥ 4.5 mEq/L. Participants will not be blind to treatment allocation. The primary endpoint is AFACS, defined as an episode of atrial fibrillation, flutter or tachycardia lasting ≥ 30 seconds until hour 120 after surgery, which is both clinically detected and electrocardiographically confirmed. Assuming a 35% incidence of AFACS in the 'tight control group', and allowing for a 10% loss to follow-up, 1684 participants are required to provide 90% certainty that the upper limit of a one-sided 97.5% confidence interval (CI) will exclude a > 10% difference in favour of tight potassium control. Secondary endpoints include mortality, use of hospital resources and incidence of dysrhythmias not meeting the primary endpoint (detected using continuous heart rhythm monitoring). DISCUSSION: The Tight K Trial will assess whether a protocol to maintain serum potassium ≥ 3.6 mEq/L is non inferior to maintaining serum potassium ≥ 4.5 mEq/L in preventing new-onset AFACS after isolated CABG. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04053816. Registered on 13 August 2019. Last update 7 January 2021.

Detecting heart failure using novel bio-signals and a knowledge enhanced neural network.

BACKGROUND: Clinical decisions about Heart Failure (HF) are frequently based on measurements of left ventricular ejection fraction (LVEF), relying mainly on echocardiography measurements for evaluating structural and functional abnormalities of heart disease. As echocardiography is not available in primary care, this means that HF cannot be detected on initial patient presentation. Instead, physicians in primary care must rely on a clinical diagnosis that can take weeks, even months of costly testing and clinical visits. As a result, the opportunity for early detection of HF is lost. METHODS AND RESULTS: The standard 12-Lead ECG provides only limited diagnostic evidence for many common heart problems. ECG findings typically show low sensitivity for structural heart abnormalities and low specificity for function abnormalities, e.g., systolic dysfunction. As a result, structural and functional heart abnormalities are typically diagnosed by echocardiography in secondary care, effectively creating a diagnostic gap between primary and secondary care. This diagnostic gap was successfully reduced by an AI solution, the Cardio-HART™ (CHART), which uses Knowledge-enhanced Neural Networks to process novel bio-signals. Cardio-HART reached higher performance in prediction of HF when compared to the best ECG-based criteria: sensitivity increased from 53.5% to 82.8%, specificity from 85.1% to 86.9%, positive predictive value from 57.1% to 70.0%, the F-score from 56.4% to 72.2%, and area under curve from 0.79 to 0.91. The sensitivity of the HF-indicated findings is doubled by the AI compared to the best rule-based ECG-findings with a similar specificity level: from 38.6% to 71%. CONCLUSION: Using an AI solution to process ECG and novel bio-signals, the CHART algorithms are able to predict structural, functional, and valve abnormalities, effectively reducing this diagnostic gap, thereby allowing for the early detection of most common heart diseases and HF in primary care.

Maintenance of Serum Potassium Levels ≥3.6 mEq/L Versus ≥4.5 mEq/L After Isolated Elective Coronary Artery Bypass Grafting and the Incidence of New-Onset Atrial Fibrillation: Pilot and Feasibility Study Results.

OBJECTIVE: Serum potassium levels frequently are maintained at high levels (≥4.5 mEq/L) to prevent atrial fibrillation after cardiac surgery (AFACS), with limited evidence. Before undertaking a noninferiority randomized controlled trial to investigate the noninferiority of maintaining levels ≥3.6 mEq/L compared with this strategy, the authors wanted to assess the feasibility, acceptability, and safety of recruiting for such a trial. DESIGN: Pilot and feasibility study of full trial protocol. SETTING: Two university tertiary-care hospitals. PARTICIPANTS: A total of 160 individuals undergoing first-time elective isolated coronary artery bypass grafting. INTERVENTIONS: Randomization (1:1) to protocols aiming to maintain serum potassium at either ≥3.6 mEq/L or ≥4.5 mEq/L after arrival in the postoperative care facility and for 120 hours or until discharge from the hospital or AFACS occurred, whichever happened first. MEASUREMENTS AND MAIN RESULTS: Primary outcomes: (1) whether it was possible to recruit and randomize 160 patients for six months (estimated 20% of those eligible); (2) maintaining supplementation protocol violation rate ≤10% (defined as potassium supplementation being inappropriately administered or withheld according to treatment allocation after a serum potassium measurement); and (3) retaining 28-day follow-up rates ≥90% after surgery. Between August 2017 and April 2018, 723 patients were screened and 160 (22%) were recruited. Potassium protocol violation rate = 9.8%. Follow-up rate at 28 days = 94.3%. Data on planned outcomes for the full trial also were collected. CONCLUSIONS: It is feasible to recruit and randomize patients to a study assessing the impact of maintaining serum potassium concentrations at either ≥3.6 mEq/L or ≥4.5 mEq/L on the incidence of AFACS.

Primary care heart failure service identifies a missed cohort of heart failure patients with reduced ejection fraction.

AIMS: We explored whether a missed cohort of patients in the community with heart failure (HF) and left ventricular systolic dysfunction (LVSD) could be identified and receive treatment optimization through a primary care heart failure (PCHF) service. METHODS AND RESULTS: PCHF is a partnership between Inspira Health, National Health Service Cardiologists and Medtronic. The PCHF service uses retrospective clinical audit to identify patients requiring a prospective face-to-face consultation with a consultant cardiologist for clinical review of their HF management within primary care. The service is delivered via five phases: (i) system interrogation of general practitioner (GP) systems; (ii) clinical audit of medical records; (iii) patient invitation; (iv) consultant reviews; and (v) follow-up. A total of 78 GP practices (864 194 population) have participated. In total, 19 393 patients' records were audited. HF register was 9668 (prevalence 1.1%) with 6162 patients coded with LVSD (prevalence 0.7%). HF case finder identified 9725 additional patients to be audited of whom 2916 patients required LVSD codes adding to the patient medical record (47% increase in LVSD). Prevalence of HF with LVSD increased from 0.7% to 1.05%. A total of 662 patients were invited for consultant cardiologist review at their local GP practice. The service found that within primary care, 27% of HF patients identified for a cardiologist consultation were eligible for complex device therapy, 45% required medicines optimization, and 47% of patients audited required diagnosis codes adding to their GP record. CONCLUSION: A PCHF service can identify a missed cohort of patients with HF and LVSD, enabling the optimization of prognostic medication and an increase in device prescription.

Inconsistent Methodology as a Barrier to Meaningful Research Outputs From Studies of Atrial Fibrillation After Cardiac Surgery.

Atrial fibrillation after cardiac surgery (AFACS) is a serious postoperative complication. There is significant research interest in this field but also relevant heterogeneity in reported AFACS definitions and approaches used for its identification. Few data exist on the extent of this variation in clinical studies. The authors reviewed the literature since 2001 and included manuscripts reporting outcomes of AFACS in adults. They excluded smaller studies and studies in which patients did not undergo a sternotomy. The documented protocol in each manuscript was analyzed according to six different categories to determine how AFACS was defined, which techniques were used to identify it, and the inclusion and/or exclusion criteria. They also noted when a category was not described in the documented protocol. The authors identified 302 studies, of which 92 were included. Sixty-two percent of studies were randomized controlled trials. There was significant heterogeneity in the manuscripts, including the exclusion of patients with preoperative AF, the definition and duration of AF needed to meet the primary endpoint, the type of screening approach (continuous, episodic, or opportunistic), the duration of monitoring during the study period in days, the diagnosis with predefined electrocardiogram criteria, and the requirement for independent confirmation by study investigators. Furthermore, the definitions of these criteria frequently were not described. Consistent reporting standards for AFACS research are needed to advance scientific progress in the field. The authors here propose pragmatic standards for trial design and reporting standards. These include adequate sample size estimation, a clear definition of the AFACS endpoints, and a protocol for AFACS detection.

Sertraline as a rare cause of interstitial lung disease.

Sertraline, a selective serotonin reuptake inhibitor, is commonly prescribed for the treatment of moderate-to-severe depression. We report a case of a 36-year-old male taking sertraline for 7 weeks prior to developing a dry cough, pleuritic chest pain, hypoxia and diffuse ground-glass attenuation with mediastinal lymphadenopathy on imaging. No infectious aetiology was identified and multiple causes of pneumonitis excluded. Sertraline-induced interstitial lung disease was subsequently diagnosed. Sertraline was discontinued and treatment commenced with a weaning course of oral dexamethasone, leading to a rapid reduction in oxygen requirement and successful discharge. Given the increasing prevalence of selective serotonin reuptake inhibitor use, it is vital that medical professionals can recognize sertraline as a rare, albeit potentially life-threatening, cause of interstitial lung disease-allowing for the rapid diagnosis and appropriate management of this condition.

Trends in referrals to liaison psychiatry teams from UK emergency departments for patients over 65.

INTRODUCTION: The number of people over the age of 65 attending Emergency Departments (ED) in the United Kingdom (UK) is increasing. Those who attend with a mental health related problem may be referred to liaison psychiatry for assessment. Improving responsiveness and integration of liaison psychiatry in general hospital settings is a national priority. To do this psychiatry teams must be adequately resourced and organised. However, it is unknown how trends in the number and type referrals of older people to liaison psychiatry teams by EDs are changing, making this difficult. METHODS: We performed a national multi-centre retrospective service evaluation, analysing existing psychiatry referral data from EDs of people over 65. We described trends in the number, rate, age, mental health presentation, and time taken to assessment over a 7 years period. RESULTS: Referral data from 28 EDs across England and Scotland were analysed (n = 18,828 referrals). There was a general trend towards increasing numbers of people referred to liaison psychiatry year on year. Variability in referral numbers between different departments, ranged from 0.1 to 24.3 per 1000 ED attendances. The most common reasons for referral were mood disorders, self-harm and suicidal ideas. The majority of referrals were assessed within 60 min, however there is variability between departments, some recording waits over 11 h. DISCUSSION: The data suggests great inter-departmental variability in referral numbers. Is not possible to establish the cause of variability. However, the data highlights the importance of asking further questions about why the differences exist, and the impact that has on patient care.

Do people living in disadvantaged circumstances receive different mental health treatments than those from less disadvantaged backgrounds?

BACKGROUND: Socio-economic status (SES) has been linked to treatment outcomes for mental health problems, whilst little to no literature has explored the effects of SES on access to both medication and psychological therapy. The aim of this study was to explore whether access to mental health treatments differed by SES. METHODS: The North West Coast Household Health Survey (HHS) collected data from residents aged 18+ from across 20 disadvantaged and 8 less disadvantaged neighbourhoods in 2015, and from 20 disadvantaged neighbourhoods in 2018. Logistic regression was used to explore the effects of SES on access to treatment (medication, psychological therapy) for people who had experienced mental health problems in the past 12 months. RESULTS: Of 6860 participants, 2932 reported experiencing mental health problems in the past 12 months. People from more disadvantaged backgrounds experienced greater rates of anxiety and depression. Anti-depressant and anti-psychotic medication treatment was significantly more common in residents with lower SES, as well as counselling. Regression analysis showed that residents from more disadvantaged neighbourhoods who reported mental distress were more likely to receive medication. CONCLUSIONS: This appears to be the first study showing higher levels of treatment with medication and psychological therapy in people from disadvantaged backgrounds. Future research needs to address the underlying factors associated with increased mental health treatment uptake in people from lower socio-economic backgrounds.

Are Serum Potassium and Magnesium Levels Associated with Atrial Fibrillation After Cardiac Surgery?

OBJECTIVES: Potassium and magnesium are frequently administered after cardiac surgery to reduce the risk of atrial fibrillation (AF). The evidence for this practice is unclear. This study was designed to evaluate the relationship between serum potassium and magnesium levels and AF after cardiac surgery. DESIGN: Observational cohort study. SETTING: A cardiac intensive care unit in the United Kingdom. PARTICIPANTS: Patients undergoing cardiac surgery between January 2013 and November 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cardiac rhythm was assessed using continuous electrocardiogram (ECG) monitoring in 3,068 patients on the cardiac intensive care unit. Associations between serum potassium and magnesium concentrations extracted from hospital databases and postoperative AF were assessed using univariable and multivariable analyses. The association between electrolyte supplementation therapy and AF was also analyzed. AF developed within 72 hours of cardiac surgery in 545 (17.8%) of the 3,068 patients. After adjusting for logistic EuroSCORE, surgery type, cardiopulmonary bypass time and age, mean serum potassium concentration <4.5 mmol/L was associated with an increased risk of AF (odds ratio [OR] 1.43 (95% confidence interval (CI): 1.17-1.75), p < 0.001). Mean magnesium concentration <1.0 mmol/L was not associated with an increased risk of AF (OR 0.89, 0.71-1.13, p = 0.342), but the administration of magnesium was associated with increased risk of developing AF (OR 1.61, 1.33-1.96, p < 0.001). CONCLUSIONS: Maintaining a serum potassium concentration ≥4.5 mmol/L after cardiac surgery may reduce the incidence of postoperative AF. Magnesium supplementation was associated with an increased risk of postoperative AF. Prospective randomized trials are required to clarify these associations.

New-Onset Atrial Fibrillation in Adult Patients After Cardiac Surgery.

PURPOSE OF REVIEW: An overview of recent literature regarding pathophysiology, risk factors, prophylaxis, and treatment of new-onset atrial fibrillation (AF) in post-cardiac surgical patients. RECENT FINDINGS: AF is the most frequent adverse event after cardiac surgery with significant associated morbidity, mortality, and financial cost. Its causes are multifactorial, and models to stratify patients into risk categories are progressing but a consistent, evidence-based system has not yet been developed. Pharmacologic and surgical interventions to prevent and treat this complication have been an area of ongoing research and recent societal guidelines reflect this. SUMMARY: Inconsistencies remain surrounding how to best identify higher-risk AF patients, which interventions should be used to prevent and treat AF, and which patient groups should receive these interventions. The evidence for these available strategies and their place in contemporary guidelines are summarized.

Brachial plexus impingement secondary to implantable cardioverter defibrillator: A case report.

Overall complication rates of 9.1% have been reported following implantable cardioverter defibrillator (ICD) placement. Brachial plexus injury is infrequently reported in the literature. We describe a 26-year-old female experiencing left arm nerve pain, a positive Tinel's sign, numbness in the median nerve distribution of the hand and biceps muscle weakness following revision ICD via subclavian vein approach. Nerve conduction studies identified severe partial left brachial plexopathy, which remained incompletely resolved with conservative management. Surgical exploration revealed lateral cord impingement by the ICD generator and a loop of the ICD lead, along with fibrosis, necessitating surgical neurolysis and ICD generator repositioning. As increasing numbers of patients undergo cardiac device implantation, it is incumbent on practitioners to be aware of potential increases in the prevalence of this complication.

Thrombo-embolic events in left ventricular endocardial pacing: long-term outcomes from a multicentre UK registry.

Aims: Endocardial left ventricular (LV) pacing is a viable alternative in patients with failed coronary sinus (CS) lead implantation. However, long-term thrombo-embolic risk remains unknown. Much of the data have come from a small number of centres. We examined the safety and efficacy of endocardial LV pacing to determine the long-term thrombo-embolic risk. Methods and results: Registries from four UK centres were combined to include 68 patients with endocardial leads with a mean follow-up of 20 months. These were compared to a matched 1:2 control group with conventional CS leads. Medical records were reviewed, and patients contacted for follow-up. Ischaemic stroke occurred in four patients (6%) in the endocardial arm providing an annual event rate (AER) of 3.6% over a 20 month follow-up; compared to 9 patients (6.6%) amongst controls with an AER of 3.4% over a 23-month follow-up. Regression analyses showed a significant association between sub-therapeutic international normalized ratio and stroke (P = 0.0001) in the endocardial arm. There was no association between lead material and mode of delivery (transatrial/transventricular) and stroke. Mortality rate was 12 and 15 per 100 patient years in the endocardial and control arm respectively with end-stage heart failure being the commonest cause. Conclusion: Endocardial LV lead in heart failure patients has a good success rate at 1.6 year follow-up. However, it is associated with a thrombo-embolic risk (which is not different from conventional CS leads) attributable to sub-therapeutic anticoagulation. Randomized control trials and studies on non-vitamin K antagonist oral anticoagulants are required to ascertain the potential of widespread clinical application of this therapeutic modality.

Association of genetic variation in telomere-related SNP and telomerase with ventricular arrhythmias in ischemic cardiomyopathy.

BACKGROUND: Telomeres are known to provide genomic stability and telomere length has been associated with cardiovascular diseases. Moreover, a higher telomerase activity has been shown to be associated with ventricular arrhythmias (VA) in ischemic cardiomyopathy. Increasing evidence suggests that genetic variation in key telomere genes has an impact on telomerase activity. Each copy of the minor allele of SNP rs12696304, at a locus including TERC (telomerase), has been associated with ∼75 base pairs reduction in mean telomere length likely mediated by an effect on TERC expression. We investigated the impact of genetic variation of this SNP on telomerase and its association with VA in ischemic cardiomyopathy patients. METHODS AND RESULTS: Ninety ischemic cardiomyopathy patients with primary prevention implantable cardioverter defibrillators (ICDs) were recruited. Thirty-five received appropriate ICD therapy for potentially fatal VA (cases), while the remaining 55 patients did not (controls). No significant differences in baseline demographics were seen between the groups. TS was measured by qPCR, telomerase activity by TRAP assay, and SNP genotyping with Taqman probes. Telomerase was highest in C homozygous allele and had a significant association with VA in this group only (C/C,C/G,G/G; P-value 0.04, 0.33, 0.43). CONCLUSION: The present study is the first to examine the association between telomerase, a SNP at a locus including TERC, and VA in ischemic cardiomyopathy patients. Homozygosity for C-allele significantly effects telomerase expression and its association with VA in this cohort. Large-scale prospective studies are required to determine if this genetic variation predisposes patients to greater arrhythmic tendency post-MI.

The impact of maintaining serum potassium ≥3.6 mEq/L vs ≥4.5 mEq/L on the incidence of new-onset atrial fibrillation in the first 120 hours after isolated elective coronary artery bypass grafting - study protocol for a randomised feasibility trial for the proposed Tight K randomized non-inferiority trial.

BACKGROUND: Atrial fibrillation (AF) occurs in approximately one in three patients after cardiac surgery, and is associated with increased short-term and long-term mortality, intensive care unit (ICU) and hospital stay, and increased cost of care. In an attempt to reduce AF incidence in these patients, serum potassium (K+) levels are commonly maintained at the high end of normal (4.5-5.5 mEq/L). However, such potassium supplementation is without proven benefit, and is not without negative consequences. It carries clinical risk, negatively impacts patient experience and is both time-consuming and costly. This protocol describes a randomised controlled pilot trial to assess the feasibility of a proposed randomised non-inferiority trial to investigate the impact of maintaining serum potassium ≥ 3.6 mEq/L vs ≥ 4.5 mEq/L on the incidence of new-onset atrial fibrillation in the first 120 hours after isolated elective coronary artery bypass grafting. METHODS: Design: this is a randomized feasibility trial as a pilot for a randomized non-inferiority trial. PARTICIPANTS: are 160 patients undergoing isolated coronary artery bypass grafting at two centres. Allocation: patients will be randomized (1:1) to protocols aiming to maintain serum potassium at either ≥ 3.6 mEq/L ("relaxed control") or ≥ 4.5 mEq/L ("tight control"). Primary analytic aim: was to assess the feasibility and acceptability of planning and delivering the intervention and trial methods to inform a full-scale non-inferiority trial. OUTCOME: the primary indicative efficacy outcome measures being field-tested are feasibility of participant recruitment and randomization, maintaining a protocol violation rate < 10%, and retaining 90% patient follow up 28 days after surgery. The primary clinical outcome measure of the future full "Tight K Study" will be incidence of AF after cardiac surgery. DISCUSSION: The Tight K Pilot will assess the feasibility of conducting the full trial, which is intended to confirm or refute the efficacy of current potassium management in preventing AF after cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03195647 . Registered on 23 May 2017. Last updated 19June 2017.

Chronic total occlusion in an infarct-related coronary artery and the risk of appropriate ICD therapies.

INTRODUCTION: Risk stratification for ventricular arrhythmias in patients with ischemic cardiomyopathy needs to be improved. Coronary chronic total occlusions in an infarct-related artery (IRA-CTOs) have been associated with an increased arrhythmic risk. This study aimed to evaluate the association between IRA-CTOs and appropriate implantable cardioverter-defibrillator (ICD) therapies. METHODS AND RESULTS: Observational cohort study that included 342 patients with ischemic cardiomyopathy, an ICD implanted for primary or secondary prevention, and a coronary angiography performed shortly before ICD implantation. The ICD was implanted for primary prevention in 163 patients (48%). IRA-CTO was found in 161 patients (47%). During a median follow-up of 33 months, 41% of patients experienced at least one appropriate ICD therapy. Patients with IRA-CTO had higher proportions of appropriate ICD therapies (57% vs. 26%, P < 0.001) and appropriate ICD shocks (40% vs. 17%, P < 0.001). At multivariate Cox regression, IRA-CTO was the only variable that consistently resulted as independent predictor of appropriate ICD therapies and shocks both in the global population of the study (HR 2.3, P < 0.001 and HR 3, P < 0.001, respectively) and when analyzing separately patients with primary or secondary prevention ICD. CONCLUSIONS: IRA-CTO is an independent predictor of appropriate ICD therapies, including appropriate ICD shocks. This association is consistent across all the subgroups analyzed. Patients with IRA-CTO have a very high risk of appropriate ICD therapies. These findings may help improving risk stratification as well as the management of ventricular arrhythmias in patients with ischemic cardiomyopathy.

Late Gadolinium Enhancement and the Risk for Ventricular Arrhythmias or Sudden Death in Dilated Cardiomyopathy: Systematic Review and Meta-Analysis.

OBJECTIVES: The aim of this study was to evaluate the association between late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging and ventricular arrhythmias or sudden cardiac death (SCD) in patients with dilated cardiomyopathy (DCM). BACKGROUND: Risk stratification for SCD in DCM needs to be improved. METHODS: A systematic review and meta-analysis were conducted. A systematic search of PubMed and Ovid was performed, and observational studies that analyzed the arrhythmic endpoint (sustained ventricular arrhythmia, appropriate implantable cardioverter-defibrillator [ICD] therapy, or SCD) in patients with DCM, stratified by the presence or absence of LGE, were included. RESULTS: Twenty-nine studies were included, accounting for 2,948 patients. The studies covered a wide spectrum of DCM, with a mean left ventricular ejection fraction between 20% and 43%. LGE was significantly associated with the arrhythmic endpoint both in the overall population (odds ratio: 4.3; p < 0.001) and when including only those studies that performed multivariate analysis (hazard ratio: 6.7; p < 0.001). The association between LGE and the arrhythmic endpoint remained significant among studies with mean left ventricular ejection fractions >35% (odds ratio: 5.2; p < 0.001) and was maximal in studies that included only patients with primary prevention ICDs (odds ratio: 7.8; p = 0.008). CONCLUSIONS: Across a wide spectrum of patients with DCM, LGE is strongly and independently associated with ventricular arrhythmia or SCD. LGE could be a powerful tool to improve risk stratification for SCD in patients with DCM. These results raise 2 major questions to be addressed in future studies: whether patients with LGE could benefit from primary prevention ICDs irrespective of their left ventricular ejection fractions, while patients without LGE might not need preventive ICDs despite having severe left ventricular dysfunction.

Cell Size Critically Determines Initial Retention of Bone Marrow Mononuclear Cells in the Heart after Intracoronary Injection: Evidence from a Rat Model.

Intracoronary injection of bone marrow mononuclear cells (BMMNC) is an emerging treatment for heart failure. Initial donor cell retention in the heart is the key to the success of this approach, but this process remains insufficiently characterized. Although it is assumed that cell size of injected cells may influence their initial retention, no scientific evidence has been reported. We developed a unique model utilizing an ex-vivo rat heart perfusion system, enabling quantitative assessment of retention of donor cells after intracoronary injection. The initial (5 minutes after intracoronary injection) retention rate of BMMNC was as low as approximately 20% irrespective of donor cell doses injected (1×106, 8×106, 4×107). Quantitative cell-size assessment revealed a positive relationship between the size of BMMNC and retention ratio; larger subpopulations of BMMNC were more preferentially retained compared to smaller ones. Furthermore, a larger cell type-bone marrow-derived mesenchymal stromal cells (median size = 11.5µm versus 7.0µm for BMMNC)-had a markedly increased retention rate (77.5±1.8%). A positive relationship between the cell size and retention ratio was also seen in mesenchymal stromal cells. Flow-cytometric studies showed expression of cell-surface proteins, including integrins and selectin-ligands, was unchanged between pre-injection BMMNC and those exited from the heart, suggesting that biochemical interaction between donor cells and host coronary endothelium is not critical for BMMNC retention. Histological analyses showed that retained BMMNC and mesenchymal stromal cells were entrapped in the coronary vasculature and did not extravasate by 60 minutes after transplantation. Whilst BMMNC did not change coronary flow after intracoronary injection, mesenchymal stromal cells reduced it, suggesting coronary embolism, which was supported by the histological finding of intravascular cell-clump formation. These data indicate that cell-size dependent, passive (mechanical), intravascular entrapment is responsible for the initial donor cell retention after intracoronary injection of BMMNC in the heart having normal vasculatures (at least).